This proposal addresses a fundamental question in hepatitis C research; what is the mechanistic role of oxidative stress in the progression of HCV infection? There is a limited knowledge on the mechanism(s) by which HCV causes liver and other types of damage. This study will test the hypothesis that oxidative stress is a mechanistic component of chronic HCV infection in Puerto Rican populations. This will serve as the first population based study that utilizes multiple markers of oxidative stress to test this hypothesis. This will be accomplished through the following aims: Specific Aim 1: The aim of these studies is to evaluate the role of the serum iron balance in the development of oxidative stress. Hypothesis: iron is a key component of oxidative stress in Puerto Ricans with chronic HCV. Specific Aim 2: The aim of these studies is to characterize the DNA adducts in leukocytes and to determine if different adducts are produced in HCV patients. Hypothesis 1: DNA adducts are markers in the chronic progression of HCV-related hepatitis. Hypothesis 2: DNA adducts are correlated with the serum iron balance. Specific Aim 3:The aim of these experiments is to evaluate whether manganese superoxide dismutase (MnSOD) is a suitable marker of oxidative stress in blood from HCV patients. Hypothesis: MnSOD specific activity is significantly increased in the leukocytes and erythrocytes of patients with chronic HCV infection. Specific Aim 4: The aim of these experiments is to determine whether patients with chronic HCV show higher plasma levels of lipid peroxidation. Hypothesis: Significantly higher levels of malonaldehyde and 4-hydroxynonenal are found in the plasma of HCV positive patients when compared with controls. Data on HCV viral genotype, viral load, disease stage, activity of liver aminotransferases, type of pharmacological treatment will be statistically analyzed to determine whether correlations exist with these markers of oxidative stress.